MCW Cardiovascular Center Stem Cells and Transgenics Affinity Group

The Cardiovascular Center has initiated AFFINITY GROUPS to stimulate and foster greater interaction and collaborations between CVC investigators and other investigators from MCW departments and outside institutions, such as Marquette University, the University of Wisconsin Milwaukee and the University of Georgia.

This affinity group brings together investigators from two basic research departments and four interdisciplinary research centers. The common theme connecting these investigators is an interest in cutting-edge technologies for answering fundamental questions about mammalian biology and disease. Aron Geurts, PhD organizes the group and focuses on generating genetically engineered rat models of human disease by altering genes in the rat genome. One technology, zinc-finger nuclease genome editing, was used to produce the world’s first “knockout rats” where specific genes are mutated to disrupt their function in order to understand their role in disease. Another approach uses jumping genes, called “transposons,” to add new genes to the rat genome to see how they impact disease processes.

Combined efforts in several labs also have goals of developing stem cell technology for engineering genetic changes in laboratory model organisms, developing tissues that can be manipulated and studied in vitro, and understanding organ development. A continuing collaboration between Dr. Geurts lab and researchers in the lab of Howard Jacob, PhD is aimed at developing stem cells from rats. Embryonic stem cells (ESCs) derived from rat embryos will be a useful tool for altering the genome sequence of the rat and generating new disease models. Members of these two groups also work closely with Stephen Duncan, DPhil toward developing induced pluripotent stem cells (iPSCs) from mice, rats, and humans. iPSCs are generated by a process called “genetic reprogramming” whereby specific genes are introduced into a differentiated cell like a skin fibroblast using viruses or transposons to cause them to turn into cells that are highly pluripotent and have the ability to develop into any cell type. These cells may allow for genome engineering in these models. They are being explored for their potential for directed differentiation of cells such as hepatocytes and cardiomyocytes, in order to understand the process by which these highly specialized, organ-specific cells develop from early embryonic precursor cells. ESCs, iPSCs, and the tissues and animals derived from them will be powerful tools for understanding gene function related to human disease, responses to environmental stress and stimuli, and developing therapeutic strategies.

Along with Drs. Geurts, Jacob, and Duncan, investigators such as Allen W. Cowley, Jr., PhD, Andrey Sorokin, PhD and Mingyu Liang, PhD collaborate to capitalize on these and other technologies by creating genetically modified rat models of hypertension and renal disease to understand how specific genes related to their lab interests play a role.

Together, the members of the CVC Stem Cells & Transgenics affinity group are working through technology to manipulate whole animal and human cell culture model systems to understand disease mechanisms and provide their expertise to other researchers who are interested in developing similar research tools.